• Female

C.-X. Yi MD PhD

Position: Scientific staff member (UD)
Main activities: Research
Specialisation: Hypothalamic neuron-glia Interaction in metabolic diseases
foto
Focus of research:

Our major research goal is to dissect the hypothalamic neuron-glia networks in regulation of energy homeostasis, at levels of intercellular communications, intracellular signaling and organelles functionality. Not until recently, we gained knowledge that the mechanism under the development of metabolic disease is beyond canonical concept that brain metabolic sensing and regulation is dominated by the role of neurons and pathways controlled by neurons. The microenvironment in which neurons live is supported and maintained by other cells. In this microenvironment, the innate immune cells, the microglia function as the immune homeostatic keeper, by clearance of debris produced by different cells and initiate immune response by releasing cytokines and chemokines. Our recent study showed that with hypercaloric challenge, microglia in the mediobasal hypothalamus adopt a proinflammatory-like state, this activation is associated with a functional changes of neuronal network involved in keeping energy balance.

Our main projects:
• Determine in rodents and human the impact of hypercaloric environment and neuronal signals on hypothalamic microglial function, to search for effective targets that can restore microglial function upon hypercaloric challenges.
• Determine in rodents and human the impact of microglia-derived factors on neuronal function, especially focusing on the effects of cytokines on neuronal mitochondria bioenergetics and dynamics as well as insulin and leptin signaling.

Our long-term goal is to search for neuronal targets that can rescue neuronal dysfunction in a hypercaloric environment and treat obesity and diabetes.
 

AMC themes: Metabolic disorders and gastrointestinal diseases
Departments: Internal Medicine: Endocrinology
Gao Y, Bielohuby M, Fleming T, Grabner GF, Foppen E, Bernhard W, Guzmán-Ruiz M, Layritz C, Legutko B, Zinser E, García-Cáceres C, Buijs RM, Woods SC, Kalsbeek A, Seeley RJ, Nawroth PP, Bidlingmaier M, Tschöp MH, Yi CX, Dietary sugars, not lipids, drive hypothalamic inflammation. MOL METAB 2017;6 (8):897-908 [PubMed]
Gao Y, Layritz C, Legutko B, Eichmann TO, Laperrousaz E, Moullé VS, Cruciani-Guglielmacci C, Magnan C, Luquet S, Woods SC, Eckel RH, Yi CX, Garcia-Caceres C, Tschöp MH, Disruption of Lipid Uptake in Astroglia Exacerbates Diet-Induced Obesity. DIABETES 2017;66 (10):2555-2563 [PubMed]
Gao Y, Vidal-Itriago A, Kalsbeek MJ, Layritz C, García-Cáceres C, Tom RZ, Eichmann TO, Vaz FM, Houtkooper RH, van der Wel N, Verhoeven AJ, Yan J, Kalsbeek A, Eckel RH, Hofmann SM, Yi CX, Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity. CELL REP 2017;20 (13):3034-3042 [PubMed]
Li Z, Yi CX, Katiraei S, Kooijman S, Zhou E, Chung CK, Gao Y, van den Heuvel JK, Meijer OC, Berbée JFP, Heijink M, Giera M, Willems van Dijk K, Groen AK, Rensen PCN, Wang Y, Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit. GUT 2017;ahead of print [PubMed]
Quarta C, Clemmensen C, Zhu Z, Yang B, Joseph SS, Lutter D, Yi CX, Graf E, García-Cáceres C, Legutko B, Fischer K, Brommage R, Zizzari P, Franklin BS, Krueger M, Koch M, Vettorazzi S, Li P, Hofmann SM, Bakhti M, Bastidas-Ponce A, Lickert H, Strom TM, Gailus-Durner V, Bechmann I, Perez-Tilve D, Tuckermann J, Hrabě de Angelis M, Sandoval D, Cota D, Latz E, Seeley RJ, Müller TD, DiMarchi RD, Finan B, Tschöp MH, Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity. CELL METAB 2017;26 (4):620-+ [PubMed]
Xiong K, Long L, Zhang X, Qu H, Deng H, Ding Y, Cai J, Wang S, Wang M, Liao L, Huang J, Yi CX, Yan J, Overview of long non-coding RNA and mRNA expression in response to methamphetamine treatment in vitro. TOXICOL IN VITRO 2017;44:1-10 [PubMed]
Yi CX, Walter M, Gao Y, Pitra S, Legutko B, Kälin S, Layritz C, García-Cáceres C, Bielohuby M, Bidlingmaier M, Woods SC, Ghanem A, Conzelmann KK, Stern JE, Jastroch M, Tschöp MH, TNF alpha drives mitochondrial stress in POMC neurons in obesity. NAT COMMUN 2017;8:15143 [PubMed]
Grabner GF, Eichmann TO, Wagner B, Gao Y, Farzi A, Taschler U, Radner FPW, Schweiger M, Lass A, Holzer P, Zinser E, Tschöp MH, Yi CX, Zimmermann R, Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide-induced Neuroinflammation. J BIOL CHEM 2016;291 (2):913-923 [PubMed]
Kalsbeek MJT, Mulder L, Yi CX, Microglia energy metabolism in metabolic disorder. MOL CELL ENDOCRINOL 2016;438 (C):27-35 [PubMed]
Müller A, Niederstadt L, Jonas W, Yi CX, Meyer F, Wiedmer P, Fischer J, Grötzinger C, Schürmann A, Tschöp M, Kleinau G, Grüters A, Krude H, Biebermann H, Ring Finger Protein 11 Inhibits Melanocortin 3 and 4 Receptor Signaling. FRONT ENDOCRINOL 2016;7:109 [PubMed]
Dinter J, Mühlhaus J, Wienchol CL, Yi CX, Nürnberg D, Morin S, Grüters A, Köhrle J, Schöneberg T, Tschöp M, Krude H, Kleinau G, Biebermann H, Inverse Agonistic Action of 3-Iodothyronamine at the Human Trace Amine-Associated Receptor 5. PLOS ONE 2015;10 (2):e0117774 [PubMed]
Kälin S, Heppner FL, Bechmann I, Prinz M, Tschöp MH, Yi CX, Hypothalamic innate immune reaction in obesity. NAT REV ENDOCRINOL 2015;11 (6):339-351 [PubMed]
Reis WL, Yi CX, Gao Y, Tschöp MH, Stern JE, Brain Innate Immunity Regulates Hypothalamic Arcuate Neuronal Activity and Feeding Behavior. ENDOCRINOLOGY 2015;156 (4):1303-1315 [PubMed]
Gao Y, Ottaway N, Schriever SC, Legutko B, García-Cáceres C, de la Fuente E, Mergen C, Bour S, Thaler JP, Seeley RJ, Filosa J, Stern JE, Perez-Tilve D, Schwartz MW, Tschöp MH, Yi CX, Hormones and Diet, but Not Body Weight, Control Hypothalamic Microglial Activity. GLIA 2014;62 (1):17-25 [PubMed]
Habegger KM, Al-Massadi O, Heppner KM, Myronovych A, Holland J, Berger J, Yi CX, Gao Y, Lehti M, Ottaway N, Amburgy S, Raver C, Müller TD, Pfluger PT, Kohli R, Perez-Tilve D, Seeley RJ, Tschöp MH, Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia. GUT 2014;63 (8):1238-1246 [PubMed]
Kalsbeek A, Bruinstroop E, Yi CX, Klieverik L, Liu J, Fliers E, Hormonal control of metabolism by the hypothalamus-autonomic nervous system-liver axis. FRONT HORM RES 2014;42:1-28 [PubMed]
Keuper M, Jastroch M, Yi CX, Fischer-Posovszky P, Wabitsch M, Tschöp MH, Hofmann SM, Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions. FASEB J 2014;28 (2):761-770 [PubMed]
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL, Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. NAT NEUROSCI 2014;17 (7):908-910 [PubMed]
Morselli E, Fuente-Martin E, Finan B, Kim M, Frank A, Garcia-Caceres C, Navas CR, Gordillo R, Neinast M, Kalainayakan SP, Li DL, Gao Y, Yi CX, Hahner L, Palmer BF, Tschöp MH, Clegg DJ, Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha. CELL REP 2014;9 (2):633-645 [PubMed]
Mühlhaus J, Dinter J, Nürnberg D, Rehders M, Depke M, Golchert J, Homuth G, Yi CX, Morin S, Köhrle J, Brix K, Tschöp M, Kleinau G, Biebermann H, Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile. INT J MOL SCI 2014;15 (11):20638-20655 [PubMed]
Habegger KM, Kirchner H, Yi CX, Heppner KM, Sweeney D, Ottaway N, Holland J, Amburgy S, Raver C, Krishna R, Müller TD, Perez-Tilve D, Pfluger PT, Obici S, DiMarchi RD, D'Alessio DA, Seeley RJ, Tschöp MH, GLP-1R Agonism Enhances Adjustable Gastric Banding in Diet-Induced Obese Rats. DIABETES 2013;62 (9):3261-3267 [PubMed]
Müller TD, Müller A, Yi CX, Habegger KM, Meyer CW, Gaylinn BD, Finan B, Heppner K, Trivedi C, Bielohuby M, Abplanalp W, Meyer F, Piechowski CL, Pratzka J, Stemmer K, Holland J, Hembree J, Bhardwaj N, Raver C, Ottaway N, Krishna R, Sah R, Sallee FR, Woods SC, Perez-Tilve D, Bidlingmaier M, Thorner MO, Krude H, Smiley D, DiMarchi R, Hofmann S, Pfluger PT, Kleinau G, Biebermann H, Tschöp MH, The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms. NAT COMMUN 2013;4:1968 [PubMed]
Yi CX, Meyer CW, Jastroch M, Leptin action in the brain: How (and when) it makes fat burn. MOL METAB 2013;2 (2):63-64 [PubMed]
Alkemade A, Yi CX, Pei L, Harakalova M, Swaab DF, la Fleur SE, Fliers E, Kalsbeek A, AgRP and NPY Expression in the Human Hypothalamic Infundibular Nucleus Correlate with Body Mass Index, Whereas Changes in alpha MSH Are Related to Type 2 Diabetes. J CLIN ENDOCR METAB 2012;97 (6):E925-E933 [PubMed]
Girault EM, Yi CX, Fliers E, Kalsbeek A, Orexins, feeding, and energy balance. PROG BRAIN RES 2012;198:47-64 [PubMed]
Müller TD, Sullivan LM, Habegger K, Yi CX, Kabra D, Grant E, Ottaway N, Krishna R, Holland J, Hembree J, Perez-Tilve D, Pfluger PT, DeGuzman MJ, Siladi ME, Kraynov VS, Axelrod DW, DiMarchi R, Pinkstaff JK, Tschöp MH, Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J PEPT SCI 2012;18 (6):383-393 [PubMed]
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW, Obesity is associated with hypothalamic injury in rodents and humans. J CLIN INVEST 2012;122 (1):153-162 [PubMed]
Wiedmer P, Chaudhary N, Rath M, Yi CX, Ananthakrishnan G, Nogueiras R, Wirth EK, Kirchner H, Schweizer U, Jonas W, Veyrat-Durebex C, Rohner-Jeanrenaud F, Schürmann A, Joost HG, Tschöp MH, Perez-Tilve D, The HPA axis modulates the CNS melanocortin control of liver triacylglyceride metabolism. PHYSIOL BEHAV 2012;105 (3):791-799 [PubMed]
Yi CX, Al-Massadi O, Donelan E, Lehti M, Weber J, Ress C, Trivedi C, Müller TD, Woods SC, Hofmann SM, Exercise protects against high-fat diet-induced hypothalamic inflammation. PHYSIOL BEHAV 2012;106 (4):485-490 [PubMed]
Yi CX, Foppen E, Abplanalp W, Gao Y, Alkemade A, la Fleur SE, Serlie MJ, Fliers E, Buijs RM, Tschöp MH, Kalsbeek A, Glucocorticoid Signaling in the Arcuate Nucleus Modulates Hepatic Insulin Sensitivity. DIABETES 2012;61 (2):339-345 [PubMed]
Yi CX, Gericke M, Krüger M, Alkemade A, Kabra DG, Hanske S, Filosa J, Pfluger P, Bingham N, Woods SC, Herman J, Kalsbeek A, Baumann M, Lang R, Stern JE, Bechmann I, Tschöp MH, High calorie diet triggers hypothalamic angiopathy. MOL METAB 2012;1 (1-2):95-100 [PubMed]
Yi CX, Heppner KM, Kirchner H, Tong J, Bielohuby M, Gaylinn BD, Müller TD, Bartley E, Davis HW, Zhao Y, Joseph A, Kruthaupt T, Ottaway N, Kabra D, Habegger KM, Benoit SC, Bidlingmaier M, Thorner MO, Perez-Tilve D, Tschöp MH, Pfluger PT, The GOAT-Ghrelin System Is Not Essential for Hypoglycemia Prevention during Prolonged Calorie Restriction. PLOS ONE 2012;7 (2):e32100 [PubMed]
Yi CX, Tschöp MH, Brain-gut-adipose-tissue communication pathways at a glance. DIS MODEL MECH 2012;5 (5):583-587 [PubMed]
Yi CX, Tschöp MH, Woods SC, Hofmann SM, High-fat-diet exposure induces IgG accumulation in hypothalamic microglia. DIS MODEL MECH 2012;5 (5):686-690 [PubMed]
Acosta-Galvan G, Yi CX, van der Vliet J, Jhamandas JH, Panula P, Angeles-Castellanos M, del Carmen Basualdo M, Escobar C, Buijs RM, Interaction between hypothalamic dorsomedial nucleus and the suprachiasmatic nucleus determines intensity of food anticipatory behavior. P NATL ACAD SCI USA 2011;108 (14):5813-5818 [PubMed]
Kalsbeek A, Scheer FA, Perreau-Lenz S, la Fleur SE, Yi CX, Fliers E, Buijs RM, Circadian disruption and SCN control of energy metabolism. FEBS LETT 2011;585 (10):1412-1426 [PubMed]
Kalsbeek A, Yi CX, Cailotto C, la Fleur SE, Fliers E, Buijs RM, Mammalian clock output mechanisms. ESSAYS BIOCHEM 2011;49 (1):137-151 [PubMed]
Rediger A, Piechowski CL, Yi CX, Tarnow P, Strotmann R, Grüters A, Krude H, Schöneberg T, Tschöp MH, Kleinau G, Biebermann H, Mutually Opposite Signal Modulation by Hypothalamic Heterodimerization of Ghrelin and Melanocortin-3 Receptors. J BIOL CHEM 2011;286 (45):39623-39631 [PubMed]
Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, Julliard K, Woods SC, Horvath TL, Sleeman MM, D'Alessio D, Obici S, Frank R, Tschöp MH, Ghrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans. J NEUROSCI 2011;31 (15):5841-5846 [PubMed]
Yi CX, Habegger KM, Chowen JA, Stern J, Tschöp MH, A Role for Astrocytes in the Central Control of Metabolism. NEUROENDOCRINOLOGY 2011;93 (3):143-149 [PubMed]
Yi CX, Heppner K, Tschöp MH, Ghrelin in eating disorders. MOL CELL ENDOCRINOL 2011;340 (1):29-34 [PubMed]
Yi CX, Kalsbeek A, Tschöp MH, Autonomic MC Sets the Metabolic Tone. CELL METAB 2011;13 (2):121-123 [PubMed]
Yi CX, Scherer T, Tschöp MH, Cajal revisited: does the VMH make us fat?. NAT NEUROSCI 2011;14 (7):806-808 [PubMed]
Kalsbeek A, Bruinstroop E, Yi CX, Klieverik LP, La Fleur SE, Fliers E, Hypothalamic control of energy metabolism via the autonomic nervous system. ANN NY ACAD SCI 2010;1212 (1):114-129 [PubMed]
Kalsbeek A, Yi CX, la Fleur SE, Buijs RM, Fliers E, SUPRACHIASMATIC NUCLEUS AND AUTONOMIC NERVOUS SYSTEM INFLUENCES ON AWAKENING FROM SLEEP. INT REV NEUROBIOL 2010;93:91-107 [PubMed]
Kalsbeek A, Yi CX, la Fleur SE, Fliers E, The hypothalamic clock and its control of glucose homeostasis. TRENDS ENDOCRIN MET 2010;21 (7):402-410 [PubMed]
Mul JD, Yi CX, van den Berg SAA, Ruiter M, Toonen PW, van der Elst MCJ, Voshol PJ, Ellenbroek BA, Kalsbeek A, la Fleur SE, Cuppen E, Pmch expression during early development is critical for normal energy homeostasis. AM J PHYSIOL-ENDOC M 2010;298 (3):E477-E488 [PubMed]
Yi CX. Hypothalamic neural networks in control of glucose homeostasis. s.l.: s.n.; 2010. 240p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Fliers E, Buijs RM; copromotor(s): Kalsbeek A, Serlie MJM)
Yi CX, la Fleur SE, Fliers E, Kalsbeek A, The role of the autonomic nervous liver innervation in the control of energy metabolism. BBA-MOL BASIS DIS 2010;1802 (4):416-431 [PubMed]
Yi CX, Sun N, Ackermans MT, Alkemade A, Foppen E, Shi J, Serlie MJ, Buijs RM, Fliers E, Kalsbeek A, Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats. DIABETES 2010;59 (7):1591-1600 [PubMed]
Yi CX, Serlie MJ, Ackermans MT, Foppen E, Buijs RM, Sauerwein HP, Fliers E, Kalsbeek A, A Major Role for Perifornical Orexin Neurons in the Control of Glucose Metabolism in Rats. DIABETES 2009;58 (9):1998-2005 [PubMed]
Yi CX, Challet E, Pévet P, Kalsbeek A, Escobar C, Buijs RM, A circulating ghrelin mimetic attenuates light-induced phase delay of mice and light-induced Fos expression in the suprachiasmatic nucleus of rats. EUR J NEUROSCI 2008;27 (8):1965-1972 [PubMed]
Buijs RM, Scheer FA, Kreier F, Yi C, Bos N, Goncharuk VD, Kalsbeek A, Organization of circadian functions: interaction with the body. PROG BRAIN RES 2006;153:341-360 [PubMed]
Key publications

Gao Y, Vidal-Itriago A, Kalsbeek MJ, Layritz C, García-Cáceres C, Tom RZ, Eichmann TO, Vaz FM, Houtkooper RH, van der Wel N, Verhoeven AJ, Yan J, Kalsbeek A, Eckel RH, Hofmann SM, Yi CX, Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity. CELL REP 2017;20 (13):3034-3042 [PubMed]
Gao Y, Bielohuby M, Fleming T, Grabner GF, Foppen E, Bernhard W, Guzmán-Ruiz M, Layritz C, Legutko B, Zinser E, García-Cáceres C, Buijs RM, Woods SC, Kalsbeek A, Seeley RJ, Nawroth PP, Bidlingmaier M, Tschöp MH, Yi CX, Dietary sugars, not lipids, drive hypothalamic inflammation. MOL METAB 2017;6 (8):897-908 [PubMed]
Yi CX, Walter M, Gao Y, Pitra S, Legutko B, Kälin S, Layritz C, García-Cáceres C, Bielohuby M, Bidlingmaier M, Woods SC, Ghanem A, Conzelmann KK, Stern JE, Jastroch M, Tschöp MH, TNF alpha drives mitochondrial stress in POMC neurons in obesity. NAT COMMUN 2017;8:15143 [PubMed]
Kälin S, Heppner FL, Bechmann I, Prinz M, Tschöp MH, Yi CX, Hypothalamic innate immune reaction in obesity. NAT REV ENDOCRINOL 2015;11 (6):339-351 [PubMed]
Gao Y, Ottaway N, Schriever SC, Legutko B, García-Cáceres C, de la Fuente E, Mergen C, Bour S, Thaler JP, Seeley RJ, Filosa J, Stern JE, Perez-Tilve D, Schwartz MW, Tschöp MH, Yi CX, Hormones and Diet, but Not Body Weight, Control Hypothalamic Microglial Activity. GLIA 2014;62 (1):17-25 [PubMed]


All Publications

Curriculum Vitae

Research experience
04/2015 - Assistant professor, research group leader, Department of Endocrinology and Metabolism, Academic Medical Center (AMC), Amsterdam, the Netherlands.
01/2012 - 03/2015 Research group leader, Division of Neurophysiology, Institute for Diabetes and Obesity, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Munich, Germany
09/2011 - 2012 Visiting scientist in the Children's Hospital Boston, Harvard Medical School, Boston, USA.
03/2010 - 12/2011 Postdoctoral fellow at Metabolic Disease Institute, Div. of Endocrinology, Diabetes and Metabolism, Dept. of Medicine, University of Cincinnati, Cincinnati OH, USA.
11/2005 - 02/2010 PhD student at the Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.

Grants
2015 Dutch Diabetes Fonds Senior Fellowship.
2014 AMC fellowship.
2010 Rubicon grant, Netherlands Organization for Scientific Research (NWO).

Scientific Awards
1. 1st Dutch Neurofederation PhD thesis prize, DN2011, May 31st 2011.
2. GOODLIFE Healthcare travel grant, the annual meeting of the Endocrine Society 2008, San Francisco, USA.
 

Research programmes
Other research related activities
  • Membership of editorial board / Editorship, MOLECULAR METABOLISM
  • Membership of editorial board / Editorship, FRONTIERS IN ENDOCRINOLOGY
Current research funding
  • AMC (Vrijgesteld)